1. Field of the Invention
The present invention is in the fields of medicine, public health, immunology, molecular biology and virology. The invention provides compositions comprising a virus-like particle (VLP) or a virus particle and at least one antigen, particularly at least one feline antigen, and more particularly at least one feline antigen that is a human allergen. In certain embodiments, the antigen is a Fel d1 antigen or a fragment thereof, covalently linked to the VLP. The invention also provides methods for producing the compositions. The compositions of the invention induce efficient immune responses, in particular antibody responses, in mammals, particularly humans. The compositions and methods of the invention are useful in the production of vaccines, in particular for the treatment and/or prevention of allergies to cat dander and other cat antigens and allergens.
2. Related Art
The domestic cat (Felis domesticus) is an important source of indoor allergens (Lau, S., et al. (2000) Lancet 356, 1392-1397). Indeed, cats are found in about 25% of households in Western countries and allergy to cats is found in a large part of the population. The severity of symptoms range from relatively mild rhinitis and conjunctivitis to potentially life-threatening asthmatic exacerbation.
Although patients are occasionally sensitised to several different molecules in cat dander and pelts, the major allergen is Fel d 1 (i.e. Felis domesticus allergen 1; formerly Cat 1, i.e. Cat allergen 1). The importance of this allergen has been emphasised in numerous studies. In fact more than 80% of cat allergic patients exhibit IgE antibodies to this potent allergen (van Ree, R., et al. (1999) J. Allergy Clin Immunol 104, 1223-1230).
Fel d1 is a 35-39 kDa acidic glycoprotein containing 10-20% N-linked carbohydrates and is found in the pelt, saliva and lachrymal glands of cats. It is formed by two non-covalently linked heterodimers. Each heterodimer consists of one 70 residue peptide (known as “chain 1”) and one 78, 85, 90 or 92 residue peptide (known as “chain 2”) which are encoded by separate genes (see Duffort, O. A., et al. (1991) Mol Immunol 28, 301-309; Morgenstern, J. P., et al; (1991) Proc Natl Acad Sci USA 88, 9690-9694 and Griffith, I. J., et al. (1992) Gene 113, 263-268).
Treatment of cat allergic patients is currently effected by desensitization therapy involving repeated injections with increasing dosages of either a crude cat dander extract or short peptides derived from Fel d1. Lilja et al and Hedlin et al have disclosed a desensitization program in the course of which crude cat dander extracts have been given to cat allergic patients (Lilja, Q, et al. (1989) J Allergy Clin Immunol 83, 37-44 and Hedlin, et al. (1991) J Allergy Clin Immunol 87, 955-964). This program took at least two to three years and the patients after three year treatment still had systemic symptoms. Using short peptides derived from Fel d1 for desensitization resulted in non-significant difference between the peptide group and the placebo group (Oldfield, W. L., et al. (2002) Lancet 360, 47-53). Efficacy was only seen when large amount (750 μg) of the short peptide was given to patients (Norman, P. S., et al. (1996) Am J Respir Crit Care Med 154, 1623-1628).
Allergic side effects, such as late asthmatic reactions, have been reported in both crude cat dander extract treatment and in short peptide treatment. Therefore, anaphylactic shock due to the injected allergen is of great safety concern for any desensitization program. Avoidance of such effect by reducing the injected amount of allergen, however, either reduces the efficacy of the treatment or prolongs the treatment. Thus, there is a great need in the field of cat-allergy treatment for alternative desensitization regimes, and hereby in particular for desensitization regimes that are able to reduce allergic symptoms, but do not trigger allergic side reaction.